Shoot growth of woody trees and shrubs is predicted by maximum plant height and associated traits

1. The rate of elongation and thickening of individual branches (shoots) varies across plant species. This variation is important for the outcome of competition and other plant-plant interactions. Here we compared rates of shoot growth across 44 species from tropical, warm temperate, and cool temperate forests of eastern Australia.2. Shoot growth rate was found to correlate with a suite of traits including the potential height of the species, xylem-specific conductivity, leaf size, leaf area per xylem cross-section, twig diameter (at 40 cm length), wood density and modulus of elasticity.3. Within this suite of traits, maximum plant height was the clearest correlate of growth rates, explaining 50 to 67% of the variation in growth overall (p p 4. Growth rates were not strongly correlated with leaf nitrogen or leaf mass per unit leaf area.5. Correlations between growth and maximum height arose both across latitude (47%, p p p p < 0.0001), reflecting intrinsic differences across species and sites

Modelling Child Poverty and Wellbeing the Treasury’s TAWA microsimulation model

Large tax–transfer microsimulation models can play a key role in guiding tax–transfer analysis and reform. This article discusses the Treasury’s microsimulation model of the tax–transfer system (the Tax and Welfare Analysis (TAWA) model), including how it is used and the standard outputs it produces. The article also considers whether these standard outputs continue to be fit for purpose. This includes a discussion of different ways of estimating poverty impacts, the role reporting should give to financial incentives to work, and the opportunities provided by improved data. This final point is particularly important for understanding take-up and the prospect for extending the model to cover non-financial measures

TGF-β mimic proteins form an extended gene family in the murine parasite Heligmosomoides polygyrus

We recently reported the discovery of a new parasite-derived protein that functionally mimics the immunosuppressive cytokine transforming growth factor (TGF)-β. The Heligmosomoides polygyrus TGF-β Mimic (Hp-TGM) shares no homology to any TGF-β family member, however it binds the mammalian TGF-β receptor and induces expression of Foxp3, the canonical transcription factor of both mouse and human regulatory T cells. Hp-TGM consists of five atypical Complement Control Protein (CCP, Pfam 00084) domains, each lacking certain conserved residues and 12–15 amino acids longer than the 60–70 amino acids consensus domain, but with a recognizable 3-cysteine, tryptophan, cysteine motif. We now report on the identification of a family of nine related Hp-TGM homologues represented in the secreted proteome and transcriptome of H. polygyrus. Recombinant proteins from five of the nine new TGM members were tested for TGF-β activity, but only two were functionally active in an MFB-F11 reporter assay, and by the induction of T cell Foxp3 expression. Sequence comparisons reveal that proteins with functional activity are similar or identical to Hp-TGM across the first three CCP domains, but more variable in domains 4 and 5. Inactive proteins diverged in all domains, or lacked some domains entirely. Testing truncated versions of Hp-TGM confirmed that domains 1–3 are essential for full activity in vitro, while domains 4 and 5 are not required. Further studies will elucidate whether these latter domains fulfill other functions in promoting host immune regulation during infection and if the more divergent family members play other roles in immunomodulation

Middle School Students’ Conceptual Understanding of Equations: Evidence from Writing Story Problems

This study investigated middle school students’ conceptual understanding of algebraic equations. 257 sixth- and seventh-grade students solved algebraic equations and generated story problems to correspond with given equations. Aspects of the equations’ structures, including number of operations and position of the unknown, influenced students’ performance on both tasks. On the story-writing task, students’ performance on two-operator equations was poorer than would be expected on the basis of their performance on one-operator equations. Students made a wide variety of errors on the story-writing task, including (1) generating story contexts that reflect operations different from the operations in the given equations, (2) failing to provide a story context for some element of the given equations, (3) failing to include mathematical content from the given equations in their stories, and (4) including mathematical content in their stories that was not present in the given equations. The nature of students’ story-writing errors suggests two main gaps in students’ conceptual understanding. First, students lacked a robust understanding of the connection between the operation of multiplication and its symbolic representation. Second, students demonstrated difficulty combining multiple mathematical operations into coherent stories. The findings highlight the importance of fostering connections between symbols and their referents

Challenges in predicting the change in the cumulative exposure of new tobacco and related products based on emissions and toxicity dose–response data

Funding: This work was funded by the Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, the Netherlands. Project number 9.7.1Many novel tobacco products have been developed in recent years. Although many may emit lower levels of several toxicants, their risk in the long term remains unclear. We previously published a method for the exposure assessment of mixtures that can be used to compare the changes in cumulative exposure to carcinogens among tobacco products. While further developing this method by including more carcinogens or to explore its application to non-cancer endpoints, we encountered a lack of data that are required for better-substantiated conclusions regarding differences in exposure between products. In this special communication, we argue the case for more data on adverse health effects, as well as more data on the composition of the emissions from tobacco products. Such information can be used to identify significant changes in relevance to health using the cumulative exposure method with different products and to substantiate regulatory decisions.Publisher PDFPeer reviewe

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Adaptation reconceptualized: "retrofitting" ongoing organizational activities with essential elements of evidence-based interventions

http://deepblue.lib.umich.edu/bitstream/2027.42/134544/1/13012_2015_Article_948.pd

The Influence of Setting on Care Coordination for Childhood Asthma

Asthma affects 7.1 million children in the United States, disproportionately burdening African American and Latino children. Barriers to asthma control include insufficient patient education and fragmented care. Care coordination represents a compelling approach to improve quality of care and address disparities in asthma. The sites of The Merck Childhood Asthma Network Care Coordination Programs implemented different models of care coordination to suit specific settings—school district, clinic or health care system, and community—and organizational structures. A variety of qualitative data sources were analyzed to determine the role setting played in the manifestation of care coordination at each site. There were inherent strengths and challenges of implementing care coordination in each of the settings, and each site used unique strategies to deliver their programs. The relationship between the lead implementing unit and entities that provided (1) access to the priority population and (2) clinical services to program participants played a critical role in the structure of the programs. The level of support and infrastructure provided by these entities to the lead implementing unit influenced how participants were identified and how asthma care coordinators were integrated into the clinical care team.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113262/1/MCAN_Settings_Manuscript_20150708.docxhttp://deepblue.lib.umich.edu/bitstream/2027.42/113262/3/MCAN_Settings_Manuscript_20150708.pdfDescription of MCAN_Settings_Manuscript_20150708.docx : Main ArticleDescription of MCAN_Settings_Manuscript_20150708.pdf : Main Article with Title Page and Abstrac

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre